ArticleThe Journal of clinical investigation2022
FOXA2 suppresses endometrial carcinogenesis and epithelial-mesenchymal transition by regulating enhancer activity.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The trial behind it
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- A transient epithelial plasticity state defines the developmental window for uterine gland specification.bioRxiv : the preprint server for biology · 2026Article
- USP54 Promotes Ferroptosis in Non-Small Cell Lung Cancer by Mediating FOXA2 Deubiquitination and Enhancing ACSL4 Transcription.The Kaohsiung journal of medical sciences · 2026Article
- Comprehensive molecular characterization identifies therapeutic vulnerabilities in ovarian clear cell carcinoma.Genome medicine · 2026Article
- Spatial transcriptomic analysis of mouse parathyroid gland cells expressing an activating variant ofJBMR plus · 2025Article
- Endometriosis in para-aortic lymph nodes without any pelvic endometriosis: the first case report, sequencing analysis and literature review.BMC women's health · 2025Review
- A distinct mechanism of epigenetic reprogramming silences PAX2 and initiates endometrial carcinogenesis.The Journal of clinical investigation · 2025Article
- Relationship Between Activating Transcription Factor 3 and Forkhead Box Protein A2 in Spinal Cord Injury and the Underlying Mechanism.Applied biochemistry and biotechnology · 2025Article
- ACAT2 negatively modulated by FOXA2 suppresses ferroptosis to expedite the aggressive phenotypes of endometrial cancer cells.Histology and histopathology · 2025Article
- FOXA2 loss results in an increase of endometriosis development and LIF reveals a therapeutic effect for endometriosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- ESR1 overexpression is a biomarker of relapse and worse prognosis in stage I endometrioid endometrial carcinoma.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2025Article
- Generation and characterization of a mouse model of conditional Chd4 knockout in the endometrial epithelium.PloS one · 2025Article
- Organoid modeling meets cancers of female reproductive tract.Cell death discovery · 2024Review
- FOXA2 Activates RND1 to Regulate Arachidonic Acid Metabolism Pathway and Suppress Cisplatin Resistance in Lung Squamous Cell Carcinoma.The clinical respiratory journal · 2024Article
- Bioengineering approaches for the endometrial research and application.Materials today. Bio · 2024Review
- FOXA1 and FOXA2: the regulatory mechanisms and therapeutic implications in cancer.Cell death discovery · 2024Review
- Wnt/β-catenin-driven EMT regulation in human cancers.Cellular and molecular life sciences : CMLS · 2024Review
- Research progress on the application of organoids in gynecological tumors.Frontiers in pharmacology · 2024Review
- Transcriptional network governing extraembryonic endoderm cell fate choice.Developmental biology · 2023Article
- MicroRNAs as the critical regulators of Forkhead box protein family during gynecological and breast tumor progression and metastasis.European journal of medical research · 2023Review
- Exosomes Derived from Hypoxic Glioma Cells Reduce the Sensitivity of Glioma Cells to Temozolomide Through Carrying miR-106a-5p.Drug design, development and therapy · 2022Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
FOXA2 encodes a transcription factor mutated in 10% of endometrial cancers (ECs), with a higher mutation rate in aggressive variants. FOXA2 has essential roles in embryonic and uterine development. However, FOXA2's role in EC is incompletely understood. Functional investigations using human and mouse EC cell lines revealed that FOXA2 controls endometrial epithelial gene expression programs regulating cell proliferation, adhesion, and endometrial-epithelial transition. In live animals, conditional inactivation of Foxa2 or Pten alone in endometrial epithelium did not result in ECs, but simultaneous inactivation of both genes resulted in lethal ECs with complete penetrance, establishing potent synergism between Foxa2 and PI3K signaling. Studies in tumor-derived cell lines and organoids highlighted additional invasion and cell growth phenotypes associated with malignant transformation and identified key mediators, including Myc and Cdh1. Transcriptome and cistrome analyses revealed that FOXA2 broadly controls gene expression programs through modification of enhancer activity in addition to regulating specific target genes, rationalizing its tumor suppressor functions. By integrating results from our cell lines, organoids, animal models, and patient data, our findings demonstrated that FOXA2 is an endometrial tumor suppressor associated with aggressive disease and with shared commonalities among its roles in endometrial function and carcinogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.